PROJECT SUMMARY - Candidate's Plans/Training: The candidate plans a career as an independent investigator focusing on laboratory research related to interstitial lung disease. Training will include formal course work in cell biology and immunology and closely mentored completion of the research protocol. Environment: The Columbia University College of Physicians and Surgeons will provide formal course work. The Department of Medicine and the Division of Pulmonary, Allergy, and Critical Care Medicine will provide research support. The sponsor, co-sponsor, collaborators, and steering committee will provide formal oversight and mentoring to see the candidate's training and project to completion. Research: Idiopathic Pulmonary Fibrosis (IPF) is a chronic illness leading to progressive scarring of the lung, with a median survival of 2.8 years from the onset of symptoms. There are no known effective therapies, except possibly lung transplantation. Fibroblastic foci, tufts of fibroblasts and myofibroblasts adjacent to injured alveolar epithelium, seen in pathologic specimens, likely represent the leading edge of disease. To identify novel mediators in IPF, mRNA was isolated from the fibroblastic foci and from patients without IPF. Gene expression profiling revealed highly significant up-regulation of methionine aminopeptidase 2 (MetAP2), an enzyme that has been implicated in cell cycle regulation, a process which is likely to be important in IPF. To study the role of MetAP2 in pulmonary fibrosis, fumagillin, a specific inhibitor of MetAP2, was tested in the bleomycin model of pulmonary fibrosis in mice. Preliminary data show that fumagillin attenuated deposition of collagen in bleomycin-exposed mice. There is a nearly 44% reduction in the number of myofibroblasts in the lungs from mice that received fumagillin compared to controls suggesting that fumagillin decreases fibrosis by decreasing the number of collagen-producing cells. The purpose of this study is to determine the role of MetAP2 in pulmonaryfibrosis. RELEVANCE - There is no known cause or cure for idiopathic pulmonary fibrosis. The ultimate goal of this study is to uncover a novel therapeutic target for the treatment of IPF.